Autism is a behavior disorder with numerous etiologies, some of which are genetic. Tuberous sclerosis is a genetic disorder with behavioral manifestations, including autism. The observed association of autism and tuberous sclerosis may be due to a common genetic etiology. The long term objective of our research is to examine the association of autism and tuberous sclerosis at the level of gene, brian, and behavior to improve our understanding of their genetics and pathophysiology and lay the groundwork for medical prevention and treatment. The specific aims of our research are: 1) to test the hypothesis that a gene or genes located or chromosome 9q34 influence tuberous sclerosis and some cases of autism. 2) To test the hypothesis that autism and tuberous sclerosis have similar aberrant brain functioning as reflected in neuropsychological test performance. Linkage of DNA markers on 9q34 with autism in families multiplex for autism and with tuberous sclerosis in families multiplex for tuberous sclerosis, will be tested to see if a gene located at this site is involved in autism and to substantiate the recently reported linkage relation of the gene for tuberous sclerosis and this location. Neurophycholigical test performance of tuberous sclerosis patients, autistic probands, and unaffected controls will be compared to evaluate the phenotypic similarity of these two disorders at the cognitive level. Similar aberrant brain functioning may be a consequence of similar mechanisms of CNS damage, similar locations of CNS damage, and/or similar delays in CNS development. Measures of each of these potential determinants of CNS insult will be evaluated through comparative studies. Specifically, a potential mechanism to be explored is dopamine-beta-hydroxylase activity potential locations of CNS damage will be assessed using neuropsychological testes, and periods of CNS insult in prenatal development will be measured by minor physical anomolies and dermatoglyphic patterning. In addition to these sub-clinical behavioral and biological measures, the frequency of DSMIII diagnosed autism and autistic-like behaviors will be determined in the tuberous sclerosis subjects, autistic subjects, and their relatives.